PIPELINE

Antisense

Antisense oligonucleotide are defined as the oligodeoxyribonucleotide (oDNA) sequence that is complementary to the DNA or RNA sequence of the target gene. Antisense RNA defined as the antisense cDNA, which is complementary to the RNA sequence of the gene.

A design of antisense can recognize precise DNA location in a gene

Antisense can be equipped to recognize a single mRNA species among a myriad of mRNAs

Antisense can discriminate between the genetic information of normal and mutated oncogenes in cancer cells.

The use of antisense oligonucleotides, as discriminating inhibitors of gene expression resulting in decrease tumor growth, offers a novel approach to the treatment of cancer. In the antisense approach, oligonucleotides complementary to specific sequences target the mRNA involved in important cellular functions and protein production. The therapeutic application of the antisense approach is currently under exploration in many different fields including oncology and immunology. Nuclease degradation is a major limitation for the use of oligonucleotides as therapeutic agents.

The strategy behind anti­sense therapy is the development of specific therapeutic agents that aim to correct the mutations and abnormal expression of cellular genes in tumor cells by decreasing gene expression, inducing degradation of target mRNA and causing premature termination of transcription. Many in vitro and in vivo studies have investigated the therapeutic efficacy of oligonucleotides and antisense RNAs. These studies have demonstrated specific inhibition of tumor cell growth by antisense therapy and have shown synergistic inhibitory effects between antisense oligonucleotides or antisense RNA and conventional chemotherapeutic drugs used in the treatment of can­cer. Antisense oligonucleotides with modifications will improve their ability to penetrate cells, bind to gene sequences and disrupt target gene function. Many delivery systems for antisense RNA and antisense oligonucle­otides have been developed, including virus vectors (retrovirus, adenovirus and adeno-associate virus) and liposomes, to carry the antisense RNA or oli­gonucleotides through the cell membrane into the cytoplasm and nucleus of the tumor cells. Various studies showed that antisense therapies directed at abnormal genes in breast cancer are potentially useful in the treat­ment of cancer. Many antisense thera­peutic strategies are under development and provide a basis for a better understanding of the mechanisms of gene regulation and growth inhibition in human can­cer. The ability to benefit from these characteristics presents a unique opportunity in treating all cancers.

The developing ability to mass produce antisense will allow the creation of antisense that will improve the regulation of gene expression, will reduce toxicity, and improve delivery systems.